Lung Metastasis and Its Clinical Implications

Introduction:

One of the most prevalent locations of cancer metastasis is the lung. Metastasis refers to the spread of tumor cells from their original sites to adjacent tissues and distant places. It is regarded as a significant cause of morbidity and mortality. Distant metastasis is an indicator of how aggressive the initial tumor is. Lung metastasis is a complicated multistep process. Detachment from primary tumor sites, invasion into arteries, capillaries, lymphatics, extravasation into the appropriate secondary location, and creation of a microenvironment are all steps of metastatic tumor cell development.

Which Forms of Cancer Spread to the Lung?

• Breast, lung, and colorectal cancer, uterine leiomyosarcoma, and head or neck squamous cell carcinomas are common malignancies that spread to the lung parenchyma.

• Colorectal, renal, lung, and lymphoma cancers are cancers that spread to the endobronchial tree of the lungs.

• Osteosarcoma and testicular tumors are two more types of cancers that can go to the lungs.

• Other uncommon malignancies metastasis to the lung include adrenal, thyroid, choriocarcinoma, and hypernephroma.

• Some tumors cannot be diagnosed and are classified as cancer of unknown primary (CUP). For example, 90 % of cancer of unknown primary (CUP) are adenocarcinomas, with squamous cell carcinomas and undifferentiated carcinomas being less common.

What Is the Etiology of Lung Metastasis?

• Tumors' histologic, genetic, and pathologic characteristics direct them to metastasize to certain places. For example, tumors spread to the lungs by hematogenous, lymphatic, or direct invasion.

• Hematogenous spread is evident in tumors that have venous drainage into the lungs, such as head and neck cancer, thyroid cancer, kidney cancer, adrenal cancer, testicular cancer, osteosarcoma, melanoma, etc.

• Lymphatic dissemination manifested itself in two ways:

1. Antegrade lymphatic invasion through the diaphragm or pleural surfaces.
2. Retrograde lymphatic spread from hilar nodal metastases.

• Lung, stomach, breast, pancreatic, uterine, rectum, and prostate cancer are examples.

• Direct spread to the pleura occurs due to hematogenous dispersion with pleural extension, lymphatic spread, or established hepatic metastases. Cancers of the lung, breast, pancreatic, and stomach are examples.

What Is the Epidemiology of Lung Metastasis?

The second most common location of metastatic focus is the lung. It is predicted that 20 to 54 % of malignant tumors originating elsewhere in the body will spread to the lungs. Patients with lung metastasis have considerably different clinical prognoses and therapeutic choices than those with original tumors. In addition, the presence of distant metastasis is significant in tumor staging. For example, distant metastasis of breast cancer reduces five-year survival from 96 % to 21 %.

What Is the Pathophysiology of Lung Metastasis?

Epithelial to Mesenchymal Transition(EMT): Epithelial stem cells undergo mesenchymal cell transformation by gradually accumulating gene mutations. These mesenchymal cells differentiate into metastatic neoplastic cells.

Tissue Stem Cells: These are thought to be the genesis of metastatic malignancies due to parallels in gene expression and biological features.

Tumor-Associated Macrophages (TAM): Particularly those in the stroma, enable tumor formation, progression, and the eventual seeding of metastasis.

Myeloid Origin Cells: Metastatic cancer cells emerge directly from myeloid origin cells or hybrid cells created by the fusion of macrophages and non-metastatic stem cells.

What Are the Signs and Symptoms of Lung Metastasis?

Lung metastasis can manifest as a single or many metastases. The signs and symptoms are as follows:

• Fatigue.

• Nausea.

• Lack of appetite.

• Pleural effusion.

• Cough.

• Hemoptysis.

• Low back pain.

• Weight loss.

• Hemoptysis (vomiting of blood).

• Dyspnea (difficulty breathing).

• Metastasis of the scalp.

• Disruptions in electrolytes.

How Is Lung Metastasis Diagnosed?

Anemia, hypercalcemia, and electrolyte imbalances are abnormal test results that indicate metastatic illness.

• Chest X-Ray - A chest X-ray is the most common first imaging test in symptomatic and known primary tumor patients. It is inexpensive and widely available. The disadvantage is that minor metastases or military dispersion are not seen.

• Computed Tomography (CT) - Computed tomography (CT) of the chest, with helical or multi-planer projection or maximum intensity projection to maximize sensitivity. Spiral CT is more sensitive than other imaging modalities because it detects metastases at a greater rate.

• Positron Emission Tomography (PET) - Positron emission tomography (PET) uses fluorodeoxyglucose (FDG) to identify metastases elsewhere in the body. PET-CT imaging is used to locate metastases precisely on a CT scan.

• Magnetic Resonance Imaging (MRI) - It is used to detect tumor invasion of the major arteries, chambers of the heart, chest wall, and spinal column, as well as to rule out synchronous liver metastases.

• Flexibletracheobronchoscopy With Endobronchial Ultrasonography (EBUS)- A typical component of the preoperative diagnostic workup is flexible tracheobronchoscopy with endobronchial ultrasonography (EBUS). It allows for the assessment of the mucosa and the confirmation of the histology of centrally positioned metastases. In addition, it aids in evaluating the status of the peribronchial and mediastinal lymph nodes when used in conjunction with endobronchial ultrasonography.

What Is the Treatment for Lung Metastasis?

• Chemotherapy- Except for a few tumors, chemotherapy is typically not curative for pulmonary metastases. For example, Cisplatin-based first-line therapy for germ-cell testicular tumors has a high long-term cure rate. It is important in the treatment of osteogenic sarcomas. Chemotherapeutic drugs given as a neoadjuvant can assist to decrease tumor burden and manage systemic metastases. Methotrexate, Cisplatin, Doxorubicin, and Ifosfamide are neoadjuvant medicines that reduce the preoperative tumor burden. After preoperative chemotherapy, approximately one-third of all lung nodules vanish. Patients were also given postoperative adjuvant chemotherapy.

• Immunotherapy- Tumours such as malignant cutaneous melanoma and renal cell carcinoma are known to react to immunotherapy. Vaccine immunotherapy for melanoma patients offers a much higher survival rate than non-surgical treatment. When opposed to typical cytotoxic chemotherapy, vaccine treatment has the benefits of long-term effectiveness and minimal toxicity.

Conclusion:

The second-most frequent pulmonary malignancy is a metastatic lung illness, affecting 20 to 54 percent of cancer patients. In addition, a subgroup of individuals with metastatic disease presents with lung illness. The complete excision of this pulmonary burden of infection can result in five-year survival rates of up to 50 %.